Disc degeneration and disc herniation are widely occuring conditions which afflict mankind and which cause disabling back and extremity pain. Intradiscal therapy for proved disc displacement is a dramatic breakthrough in the treatment of this common disorder resulting in shorter and less costly hospitalization than cases where surgical intervention is required.
In 1963, Smith, Garvin and Jennings described the pharmacology of an enzyme that would dissolve the herniated disc that causes leg pain by compressing spinal nerves. That enzyme was chymopapain, a material derived from the fruit of the papaya plant. Over a period of twenty years, chymopapain wended its way through the complex four phases of testing prescribed by the Food and Drug Administration and over 40,000 patients have been treated by chemonucleolysis with chymopapain. The approval process was more difficult than normal due to criticism and controversies among the researchers. In 1982, the FDA approved for commercial release Smith Laboratories' Chymodiactin and Travenol's Discase brands of chymopapain.
A 1977 study by Watts of 13,700 patients injected with chymopapain showed an approximately 3% complications rate, including anaphylactic response, neurotoxicity, cardiovascular and other complications resulting in eight deaths. Nevertheless, careful analysis of these data leads to the conclusion that enzyme injection is at least five times safer than laminectomy for patients who do not show improvement after at least two months of conservative treatment and at least two weeks of bedrest, the population for which some form of intervention is indicated.
The concerns about sensitivity reactions to chymopapain led to a search for alternative chemical materials which would act in the same or similar manner on the nucleus pulposus, thereby relieving sciatic pain and other symptoms. Sussman described such a material, collagenase, in his U.S. Pat. No. 3,678,158 issued July 18, 1972. His research showed higher dissolution effect without systemic sensitivity reaction in any of the patients. While collagenase appears to have a good margin of safety at the effective dosage rates and a comparable or reduced complications rate, when compared with chymopapain, post-injection pain, both local and referred, apears more severe with collagenase than with chymopapain, suggesting that the ideal enzyme for chemonucleolysis is still to be identified. The present invention identifies a class of cartilage-dissolving enzymes of bacterial origin which appear to be less allergenic and less neurotoxic than chymopapain and at the same time will not disturb the stabilizing collagen components of disc materials.
An advantage of chondroitinase is that it removes the swelling capacity of the disc, which then shrinks, without interfering with the structural portion of the disc. In contrast, chymopapain has a proteolytic activity which may be responsible for its neurotoxicity; while collagenase dissolves the structural portion of the disc, it promotes tissue swelling which may be responsible for post injection pain nerve compression.
It is anticipated chondroitinase will be non-allergenic, as compared to chymopapain, because it is unlikely that a relatively high percentage of the population will be presensitized to it as is the case with chymopapain. Chymopapain is a plant protein that is phylogenetically more remote from mammals than chondroitenases which are of bacterial origin.